1. Field of the Invention
The invention relates to devices for continuously measuring the concentrations of more than one target analyte. Specifically, the devices comprise a plurality of analyte binding domains, with each domain being capable of specifically and reversibly binding to at least one of the target analytes. The devices further comprise a membrane surrounding these binding domains that is permeable to the target analytes. The devices convey binding information to a detector. The invention also relates to methods of using the devices, including monitoring chronic disease states in an individual.
2. Background of the Invention
Glucose is the most monitored energy metabolite for diagnosis and management of diabetes today. Indeed, maintaining blood glucose within the “normal” range of 70 to 120 mg/dL using intensive insulin therapy, and increased glucose monitoring, can significantly improve the long-term health of diabetes patients. While incremental advances have steadily been made in glucose monitor performance, most of the monitors available today still require the extraction of blood from patients, and the analysis of glucose levels by a separate monitor. The limitations of this technology are well known (pain, inconvenience, and non-compliance, primarily). Furthermore, current reaction-based sensors typically rely on an enzymatic reaction that may include cofactors, mediators, reactive products (e.g., hydrogen peroxide), or co-substrates (e.g., oxygen), which often complicates sensor development and performance analysis. A more desirable sensor, from a subject's and physician's point of view, would be a more reliable device that is not subject to numerous complications, as well as a device that has a long in vivo lifetime, is capable of quantitatively assessing glucose concentration at regular (short) intervals, and requires a minimal number of calibrations using finger-prick blood samples.
While monitoring glucose is critical for the survival of anyone with diabetes, glucose levels alone provide insufficient data for understanding the complex and dynamic metabolic processes underlying this disease and its development. While glucose is the primary energy-generating metabolite used by the brain, the majority of a day's energy is generated by tissue metabolism of fatty acids. Hence, real-time monitoring of both glucose and fatty acid levels provides greater information on one's metabolic state and will likely be important for understanding and normalizing metabolism. Fatty acid monitoring may be particularly important for understanding the events leading to early development of a pre-diabetic state or insulin resistance, particularly in Type 2 diabetes.
Similarly, minimally invasive metabolite monitors could be desirable for other applications, such as monitoring the fatigue levels in athletes or soldiers. Indeed, exercise also impacts a subjects metabolic state, and lactate, a by-product of moderate to intense exercise, acts as a marker for energy expenditure as well as exercise burden. Hence, changes in lactate concentration signify alterations in glucose metabolism as well. Coordinated use of glucose, lactate, and fatty acid sensors could therefore lead to devices that more precisely monitor fatigue and exhaustion. Continued monitoring of multiple metabolites for example, would allow athletes or soldiers to maintain improved readiness and decrease recovery times after exertion.
Currently, there is no sensor that continuously monitors in vivo metabolites. Furthermore, of the single-metabolite sensors currently available, none measure more than one metabolite directly. Accordingly, there is a need in the art for a sensor that monitors multiple metabolites and does so in a minimally invasive or painful manner. Further, the multianalyte biosensor should be designed such that it is free of complications, such as enzyme by-products.